WO2018015975A1 - Amorphous solid dispersion of selexipag - Google Patents

Amorphous solid dispersion of selexipag Download PDF

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Publication number
WO2018015975A1
WO2018015975A1 PCT/IN2017/050300 IN2017050300W WO2018015975A1 WO 2018015975 A1 WO2018015975 A1 WO 2018015975A1 IN 2017050300 W IN2017050300 W IN 2017050300W WO 2018015975 A1 WO2018015975 A1 WO 2018015975A1
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Prior art keywords
selexipag
corn starch
solid dispersion
amorphous solid
solution
Prior art date
Application number
PCT/IN2017/050300
Other languages
French (fr)
Inventor
Rajamannar Thennati
Shriprakash Dhar DWIVEDI
Arunkumar Gulabsingh Yadav
Nischalkumar Vinodbhai Patel
Bhavna Nikhil TAILOR
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Sun Pharmaceutical Industries Limited
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Publication of WO2018015975A1 publication Critical patent/WO2018015975A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds

Definitions

  • the present invention relates to an amorphous solid dispersion comprising selexipag and corn starch and process for preparation thereof.
  • UPTRAVI ® is selective non-prostanoid IP prostacyclin receptor agonist, approved in December 2015 in the United States and marketed under the brand name UPTRAVI ® as oral tablets.
  • UPTRAVI ® is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.
  • PAH pulmonary arterial hypertension
  • the United States patent No. 7,205,302 discloses selexipag and process for preparation thereof. Selexipag is reported to be present in various polymorphic forms in the literature.
  • the United States patent No. 8,791,122 discloses polymorphic forms I, II and III of selexipag.
  • the present invention provides an amorphous solid dispersion comprising selexipag and corn starch.
  • the present invention also provides a process for the preparation of amorphous solid dispersion comprising selexipag and corn starch, wherein the process comprises:
  • step a (b) adding an acid sufficient to neutralize the base, to the solution of step a,
  • the amorphous solid dispersion of selexipag of the present invention is free flowing, easy to handle which makes it suitable for manufacturing of pharmaceutical finished dosage formulations.
  • Figure 1 XRPD (X-ray powder diffraction) graph of amorphous solid dispersion of selexipag with corn starch (1 :2) obtained in example 1.
  • Figure 2 XRPD graph of amorphous solid dispersion of selexipag with corn starch (1:5) obtained in example 2.
  • Figure 3 XRPD graph of amorphous solid dispersion of selexipag with corn starch (1 :5) after 6 months storage at 25 °C to 30 °C.
  • the present invention provides an amorphous solid dispersion
  • the present invention provides an amorphous solid dispersion comprising selexipag and corn starch, wherein the ratio of selexipag to corn starch is 1 : 1 to 1 :100. In another embodiment, the ratio selexipag to corn starch is 1 :2 to 1 : 100. In a preferred embodiment, the ratio of selexipag to corn starch is 1 :2. In yet another preferred embodiment, the ratio of selexipag to corn starch is 1:5.
  • the present invention provides an amorphous solid dispersion comprising selexipag and corn starch characterized by X-ray powder diffraction pattern as shown in figure 1, figure 2 or figure 3.
  • the present invention provides an uniform amorphous solid dispersion comprising selexipag and corn starch, wherein the ratio of selexipag to corn starch is 1 :2 to 1 : 100 and wherein the said amorphous solid dispersion is stable when stored at 25 °C to 30 °C for at least 6 months.
  • stable refers to a state of a solid phase of a material, which is stable in terms of chemical stability and polymorphic form stability for atleast a period as described herein.
  • the amorphous solid dispersion comprising selexipag and corn starch of the present invention was found to be stable during storage.
  • the XRPD of the amorphous solid dispersion of the present invention does not change significantly when it was stored at 25 °C to 30 °C for more than 6 months ( Figure 3), i.e. no crystallinity was detected by X-ray analysis method. Even there was no significant change in the HPLC purity of the amorphous solid dispersion after 6 months of storage.
  • the present invention provides a process for the preparation of an amorphous solid dispersion comprising selexipag and corn starch, wherein the process comprises:
  • step a (b) adding an acid sufficient to neutralize the base to the solution of step a,
  • a suspension of selexipag in water is prepared, to which an aqueous solution of a base is added to dissolve selexipag.
  • selexipag as such can be added to an aqueous solution of a base to prepare the aqueous solution comprising selexipag and the base.
  • the base can be selected from inorganic or organic bases.
  • the inorganic base can be selected from a group comprising hydroxides and carbonates of alkali metals or alkali earth metals, for example sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate or a mixture thereof.
  • the organic base can be selected from a group comprising of triethylamine, diisopropylamine, diisopropylethylamine (DIPEA), pyridine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), l,4-diazabicyclo[2.2.2]octane (DABCO) or a mixture thereof.
  • the preferred base is sodium hydroxide.
  • the acid used in the above process may be selected from organic or inorganic acids such as hydrochloric acid, sulfuric acid, acetic acid, formic acid and the like.
  • the preferred acid is hydrochloric acid.
  • the acid may be diluted with the water or it may be used without dilution.
  • the acid may be added at a temperature ranging from 0 °C to 35 °C.
  • the aqueous solution comprising of selexipag and the base may be added to the acid.
  • the acid is used in a quantity sufficient enough to neutralize the base and precipitate the selexipag from the solution to form a suspension of selexipag in water; more preferably it is used in a quantity to adjust the pH of the solution from 5 to 7.
  • Selexipag is used in amounts such that it is precipitated out of the solution.
  • the amount of selexipag is 0.2 g to about 10 g per 100 mL of solution.
  • the amount of selexipag is about 1 g to about 8 g per 100 mL of the solution.
  • the amount of selexipag is about 2 g to about 5 g per 100 mL of solution.
  • Corn starch is added to the suspension formed in step b and the resultant suspension may be stirred at 0 °C to 35 °C to form a suspension of amorphous solid dispersion of selexipag with corn starch in water.
  • the corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1: 1 to 1 : 100.
  • corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1 :2 to 1: 100.
  • corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1 :2.
  • corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1 :5.
  • the amorphous solid dispersion comprising selexipag and corn starch may be isolated from the above suspension by well-known techniques in the art such as filtration or centrifugation. The obtained amorphous dispersion may be additionally washed with water and dried under vacuum at a temperature of 40 °C to 50 °C.
  • Selexipag used as a starting material for the process for the preparation of amorphous solid dispersion of selexipag can be prepared by any of the processes known in the art, for instance, by the process reported in United States patent No. 7,205,302.
  • the present invention provides a pharmaceutical composition comprising amorphous solid dispersion of selexipag with corn starch and one or more pharmaceutically acceptable excipient.
  • X-ray powder diffraction analyses were carried out on a PANalytical Empyrean X-ray powder diffractometer using Cu K alpha radiation.
  • the instrument was equipped with a line focus X-ray tube, and the voltage and amperage were set to 45 kV and 40 mA respectively.
  • the scanning rate was set as 10 second per step and step size is set as 0.01°.
  • the diffractometer was equipped with Pixcel 1D solid state detector and rotating sample stage.
  • X- ray diffractometer was used to record diffractogram from 4° to 40° (2-theta).
  • Example 1 Preparation of amorphous solid dispersion of selexipag with corn starch (1:2)
  • Aqueous sodium hydroxide solution (prepared by dissolving 42.2 mg sodium hydroxide in 4.2 mL of water) was added to a suspension selexipag (500 mg) in water (20 mL) at room temperature to get clear solution.
  • the solution was cooled to 0 °C to 5 °C and then aqueous hydrochloric acid solution (prepared by adding 0.11 mL concentrated HCl in 1.1 mL of water) was added to get a suspension.
  • Corn starch (lg, Unipure FL) was added and the resultant suspension was stirred for about 1 hour at room temperature. The solid was filtered and washed with water. The obtained amorphous solid dispersion was dried under vacuum at 50 °C.
  • XRPD graph is shown in Figure 1.
  • Example 2 Preparation of amorphous solid dispersion of selexipag with corn starch
  • Aqueous sodium hydroxide solution prepared by dissolving 4.2 g sodium hydroxide in 42 mL of water
  • a suspension selexipag 50 g
  • aqueous hydrochloric acid solution prepared by adding 12.85 mL concentrated HC1 in 65 mL of water
  • Corn starch 250 g, Unipure FL
  • the resultant suspension was stirred for about 1 hour at room temperature.
  • the solid was filtered and washed with water.
  • the obtained amorphous solid dispersion was dried under vacuum at 45 °C.
  • XRPD graph is shown in Figure 2.
  • HPLC purity of amorphous solid dispersion was determined by using:
  • Mobile phase Mobile phase A- buffer preparation: methanol: acetonitrile (70:20:10); Mobile phase B- buffer preparation: acetonitrile (30:70).
  • Buffer preparation was prepared by dissolving potassium dihydrogen orthophophosphate (3.4 g) in 1000 mL of water, followed by addition of triethylamine (10 mL) and adjusting the pH to 3.0 ⁇ 0.05 with orthophosphoric acid.

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  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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Abstract

The present invention relates to an amorphous solid dispersion comprising selexipag and corn starch and process for preparation thereof.

Description

AMORPHOUS SOLID DISPERSION OF SELEXIPAG
RELATED APPLICATIONS
This application claims the benefit of Indian Patent Application no. IN 201621025081 filed on July 22, 2016; which is hereby incorporated by reference.
FIELD OF THE INVENTION
The present invention relates to an amorphous solid dispersion comprising selexipag and corn starch and process for preparation thereof.
BACKGROUND OF THE INVENTION
Selexipag chemically known as 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl) amino] butoxy}- N-(methylsulfonyl)acet la I:
Figure imgf000002_0001
Formula I
Selexipag is selective non-prostanoid IP prostacyclin receptor agonist, approved in December 2015 in the United States and marketed under the brand name UPTRAVI® as oral tablets. UPTRAVI® is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.
The United States patent No. 7,205,302 discloses selexipag and process for preparation thereof. Selexipag is reported to be present in various polymorphic forms in the literature. The United States patent No. 8,791,122 (the Ί22 patent) discloses polymorphic forms I, II and III of selexipag.
SUMMARY OF THE INVENTION The present invention provides an amorphous solid dispersion comprising selexipag and corn starch.
The present invention also provides a process for the preparation of amorphous solid dispersion comprising selexipag and corn starch, wherein the process comprises:
(a) dissolving selexipag in an aqueous solution of a base,
(b) adding an acid sufficient to neutralize the base, to the solution of step a,
(c) adding corn starch, and
(d) isolating amorphous solid dispersion comprising selexipag and corn starch.
The amorphous solid dispersion of selexipag of the present invention is free flowing, easy to handle which makes it suitable for manufacturing of pharmaceutical finished dosage formulations. BRIEF DESCRIPTION OF DRAWINGS
Figure 1 : XRPD (X-ray powder diffraction) graph of amorphous solid dispersion of selexipag with corn starch (1 :2) obtained in example 1. Figure 2: XRPD graph of amorphous solid dispersion of selexipag with corn starch (1:5) obtained in example 2.
Figure 3: XRPD graph of amorphous solid dispersion of selexipag with corn starch (1 :5) after 6 months storage at 25 °C to 30 °C.
DETAILED DESCRIPTION OF THE INVENTION
Thus in one aspect, the present invention provides an amorphous solid dispersion
comprising selexipag and corn starch.
In one embodiment, the present invention provides an amorphous solid dispersion comprising selexipag and corn starch, wherein the ratio of selexipag to corn starch is 1 : 1 to 1 :100. In another embodiment, the ratio selexipag to corn starch is 1 :2 to 1 : 100. In a preferred embodiment, the ratio of selexipag to corn starch is 1 :2. In yet another preferred embodiment, the ratio of selexipag to corn starch is 1:5.
In another embodiment, the present invention provides an amorphous solid dispersion comprising selexipag and corn starch characterized by X-ray powder diffraction pattern as shown in figure 1, figure 2 or figure 3.
In another embodiment, the present invention provides an uniform amorphous solid dispersion comprising selexipag and corn starch, wherein the ratio of selexipag to corn starch is 1 :2 to 1 : 100 and wherein the said amorphous solid dispersion is stable when stored at 25 °C to 30 °C for at least 6 months.
The term "stable" as used herein refers to a state of a solid phase of a material, which is stable in terms of chemical stability and polymorphic form stability for atleast a period as described herein.
The amorphous solid dispersion comprising selexipag and corn starch of the present invention was found to be stable during storage. For instance, the XRPD of the amorphous solid dispersion of the present invention does not change significantly when it was stored at 25 °C to 30 °C for more than 6 months (Figure 3), i.e. no crystallinity was detected by X-ray analysis method. Even there was no significant change in the HPLC purity of the amorphous solid dispersion after 6 months of storage.
In another aspect, the present invention provides a process for the preparation of an amorphous solid dispersion comprising selexipag and corn starch, wherein the process comprises:
(a) dissolving selexipag in an aqueous solution of a base,
(b) adding an acid sufficient to neutralize the base to the solution of step a,
(c) adding corn starch, and
(d) isolating amorphous solid dispersion comprising selexipag and corn starch.
A suspension of selexipag in water is prepared, to which an aqueous solution of a base is added to dissolve selexipag. Alternatively, selexipag as such can be added to an aqueous solution of a base to prepare the aqueous solution comprising selexipag and the base. The base can be selected from inorganic or organic bases. The inorganic base can be selected from a group comprising hydroxides and carbonates of alkali metals or alkali earth metals, for example sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate or a mixture thereof. The organic base can be selected from a group comprising of triethylamine, diisopropylamine, diisopropylethylamine (DIPEA), pyridine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), l,4-diazabicyclo[2.2.2]octane (DABCO) or a mixture thereof. The preferred base is sodium hydroxide.
The acid used in the above process may be selected from organic or inorganic acids such as hydrochloric acid, sulfuric acid, acetic acid, formic acid and the like. The preferred acid is hydrochloric acid. The acid may be diluted with the water or it may be used without dilution. The acid may be added at a temperature ranging from 0 °C to 35 °C. Alternatively, the aqueous solution comprising of selexipag and the base may be added to the acid. The acid is used in a quantity sufficient enough to neutralize the base and precipitate the selexipag from the solution to form a suspension of selexipag in water; more preferably it is used in a quantity to adjust the pH of the solution from 5 to 7. Selexipag is used in amounts such that it is precipitated out of the solution. In one embodiment, the amount of selexipag is 0.2 g to about 10 g per 100 mL of solution. In another embodiment, the amount of selexipag is about 1 g to about 8 g per 100 mL of the solution. In yet another embodiment, the amount of selexipag is about 2 g to about 5 g per 100 mL of solution.
Corn starch is added to the suspension formed in step b and the resultant suspension may be stirred at 0 °C to 35 °C to form a suspension of amorphous solid dispersion of selexipag with corn starch in water. The corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1: 1 to 1 : 100. In another embodiment, corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1 :2 to 1: 100. In a preferred embodiment, corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1 :2. In yet another preferred embodiment, corn starch is used in a quantity wherein the ratio of selexipag to corn starch is 1 :5. The amorphous solid dispersion comprising selexipag and corn starch may be isolated from the above suspension by well-known techniques in the art such as filtration or centrifugation. The obtained amorphous dispersion may be additionally washed with water and dried under vacuum at a temperature of 40 °C to 50 °C. Selexipag used as a starting material for the process for the preparation of amorphous solid dispersion of selexipag can be prepared by any of the processes known in the art, for instance, by the process reported in United States patent No. 7,205,302. In another aspect, the present invention provides a pharmaceutical composition comprising amorphous solid dispersion of selexipag with corn starch and one or more pharmaceutically acceptable excipient.
The present invention is further illustrated in detail with reference to the following examples. It is desired that the examples be considered in all respect as illustrative and are not intended to limit the scope of the claimed invention.
EXAMPLES
Instrument details:
X-ray powder diffraction analyses were carried out on a PANalytical Empyrean X-ray powder diffractometer using Cu K alpha radiation. The instrument was equipped with a line focus X-ray tube, and the voltage and amperage were set to 45 kV and 40 mA respectively. The scanning rate was set as 10 second per step and step size is set as 0.01°. The diffractometer was equipped with Pixcel1D solid state detector and rotating sample stage. X- ray diffractometer was used to record diffractogram from 4° to 40° (2-theta).
Example 1: Preparation of amorphous solid dispersion of selexipag with corn starch (1:2)
Aqueous sodium hydroxide solution (prepared by dissolving 42.2 mg sodium hydroxide in 4.2 mL of water) was added to a suspension selexipag (500 mg) in water (20 mL) at room temperature to get clear solution. The solution was cooled to 0 °C to 5 °C and then aqueous hydrochloric acid solution (prepared by adding 0.11 mL concentrated HCl in 1.1 mL of water) was added to get a suspension. Corn starch (lg, Unipure FL) was added and the resultant suspension was stirred for about 1 hour at room temperature. The solid was filtered and washed with water. The obtained amorphous solid dispersion was dried under vacuum at 50 °C. XRPD graph is shown in Figure 1.
Example 2: Preparation of amorphous solid dispersion of selexipag with corn starch Aqueous sodium hydroxide solution (prepared by dissolving 4.2 g sodium hydroxide in 42 mL of water) was added to a suspension selexipag (50 g) in water (2.50 L) at room temperature to get clear solution. The solution was cooled to 5 °C to 10 °C and then aqueous hydrochloric acid solution (prepared by adding 12.85 mL concentrated HC1 in 65 mL of water) was added to get a suspension. Corn starch (250 g, Unipure FL) was added and the resultant suspension was stirred for about 1 hour at room temperature. The solid was filtered and washed with water. The obtained amorphous solid dispersion was dried under vacuum at 45 °C. XRPD graph is shown in Figure 2.
HPLC purity: 99.67 %.
Total Impurity content: 0.33 %.
HPLC purity of amorphous solid dispersion was determined by using:
Column: Agilent Poroshell® 120 EC C-18, (150 x 4.6) mm, 2.7μηι;
Mobile phase: Mobile phase A- buffer preparation: methanol: acetonitrile (70:20:10); Mobile phase B- buffer preparation: acetonitrile (30:70).
Buffer preparation was prepared by dissolving potassium dihydrogen orthophophosphate (3.4 g) in 1000 mL of water, followed by addition of triethylamine (10 mL) and adjusting the pH to 3.0 ± 0.05 with orthophosphoric acid.
The above amorphous solid dispersion of selexipag with corn starch (1 :5) was stored at 25 °C to 30 °C for 6 months.
XRPD graph after 6 months of storage is shown in Figure 3.
HPLC purity after 6 months of storage: 99.47 %.
Total impurity content after 6 months of storage: 0.53 %.

Claims

Claims:
An amorphous solid dispersion comprising selexipag and corn starch.
The amorphous solid dispersion as claimed in claim 1, wherein the ratio of selexipag to corn starch is 1 :2 to 1 :100.
An uniform amorphous solid dispersion comprising selexipag and corn starch, wherein the ratio of selexipag to corn starch is 1 :2 to 1 : 100 and wherein the said amorphous solid dispersion is stable when stored at 25 °C to 30 °C for at least 6 months.
A process for the preparation of amorphous solid dispersion comprising selexipag and corn starch, wherein the process comprises:
(a) dissolving selexipag in an aqueous solution of a base,
(b) adding an acid sufficient to neutralize the base, to the solution of step a,
(c) adding corn starch, and
(d) isolating amorphous solid dispersion comprising selexipag and corn starch.
The process as claimed in claim 4, wherein the ratio of selexipag to corn starch is 1 :2 to 1 :100.
PCT/IN2017/050300 2016-07-22 2017-07-21 Amorphous solid dispersion of selexipag WO2018015975A1 (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019098300A1 (en) 2017-11-16 2019-05-23 日本新薬株式会社 Controlled release formulation
WO2023195955A1 (en) * 2022-04-05 2023-10-12 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi A film coated tablet comprising selexi̇pag and its preparation process
WO2023195956A1 (en) * 2022-04-05 2023-10-12 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi A film coated tablet comprising selexi̇pag and at least one filler

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7205302B2 (en) * 2001-04-26 2007-04-17 Nippon Shinyaku Co., Ltd. Heterocyclic compound derivatives and medicines

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7205302B2 (en) * 2001-04-26 2007-04-17 Nippon Shinyaku Co., Ltd. Heterocyclic compound derivatives and medicines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MISHRA DK ET AL.: "Amorphous solid dispersion technique for improved drug delivery: basics to clinical applications", DRUG DELIV TRANSL RES, vol. 5, no. 6, December 2015 (2015-12-01), pages 552 - 565, XP035968796 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019098300A1 (en) 2017-11-16 2019-05-23 日本新薬株式会社 Controlled release formulation
WO2023195955A1 (en) * 2022-04-05 2023-10-12 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi A film coated tablet comprising selexi̇pag and its preparation process
WO2023195956A1 (en) * 2022-04-05 2023-10-12 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi A film coated tablet comprising selexi̇pag and at least one filler

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